Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

• Sponsor: Kiadis Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02500550
• Collaborator: (none)
• Enrollment: 15
• Locations: 11
• Arm: 1
• Actual Duration (Months): 38.3
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether a repeat dose administration of ATIR101 is safe and effective when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor. All patients are planned to receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or halted for safety reasons.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome	Biological: ATIR101; Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT); Procedure: TBI regime; Procedure: Non-TBI regime	Phase 2

Detailed Description

Study CR-AIR-008 is an exploratory, open-label, multicenter study. After signing informed consent, patients will receive a hematopoietic stem cell transplantation (HSCT) from a related, haploidentical donor, followed by a first ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 28 and 32 days after the HSCT. Patients will receive a second ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 70 and 74 days after the HSCT. To evaluate safety of the second dose administration, the first 6 patients treated will be evaluated for the occurrence of dose limiting toxicity (DLT), defined as acute GvHD grade III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in case of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the remaining 9 patients will continue with two ATIR101 doses of 2×10E6 viable T cells/kg. If within the first 6 patients at least 2 patients show DLT, the second ATIR101 infusion will be adjusted to a dose of 1×10E6 viable T cells/kg. If in one of the next 3 patients treated at this lower dose again DLT is observed, the second ATIR101 infusion will be halted and the remaining patients will be given only a single dose of ATIR101.

All patients treated with ATIR101 will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of the first ATIR101 infusion (Week 4) until 6 weeks after the second ATIR101 infusion (Week 16), at monthly visits from 4 until 6 months after the HSCT, and every 3 months from 6 until 12 months after the HSCT.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of a Two-dose Regimen of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells (Using Photodynamic Treatment), in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
• Actual Study Start Date: Oct 9, 2015
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Dec 17, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ATIR101

Biological: ATIR101; T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).; Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT); CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details); Procedure: TBI regime; Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.; Procedure: Non-TBI regime; Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

Outcome Measures

Primary Outcome Measures

1. Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV [180 days post HSCT]

Secondary Outcome Measures

1. Incidence and Severity of Acute and Chronic GVHD [Between 6 and 12 months after HSCT]

2. Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT [6 and 12 months post HSCT]

   Defined as CD3+ in peripheral blood higher than 0.2×10E9/L at 6 and 12 months post HSCT.

3. Viral, Fungal, and Bacterial Infections [From 6 months to 1 year after HSCT]

   Infection was defined as (1) a clinically apparent infectious disease with symptoms or (2) a viral reactivation. Severity was graded according to CTCAE vs. 4.0

4. Transplant-related Mortality (TRM) [12 months post HSCT]

   Defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide)

5. Relapse-related Mortality (RRM) [12 months post HSCT]

   Defined as death due to disease relapse or disease progression

6. Overall Survival (OS) [12 months post HSCT]

   Defined as the time from HSCT until death from any cause

7. Progression-free Survival (PFS) [12 months post HSCT]

   Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first

8. GVHD-free, Relapse-free Survival (GRFS) [12 months post HSCT]

   Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Any of the following hematologic malignancies:

• Acute myeloid leukemia (AML) in first remission with high-risk features or in second or higher remission

• Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission

• Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher IPSS-R risk group

• Karnofsky performance status ≥ 70%

• Eligible for haploidentical stem cell transplantation according to the investigator

• Male or female, age ≥ 18 years and ≤ 65 years

Exclusion Criteria:

• Availability of a fully matched related or unrelated donor following a donor search

• Diffusing capacity for carbon monoxide (DLCO) < 50% predicted

• Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA)

• AST > 2.5 x ULN (CTCAE grade 2)

• Bilirubin > 1.5 x ULN (CTCAE grade 2)

• Creatinine clearance < 50 mL/min (calculated or measured)

• Positive HIV test

• Positive pregnancy test (women of childbearing age only)

• Prior allogeneic HSCT

• Estimated probability of surviving less than 3 months

• Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)

• Known presence of HLA antibodies against the non-shared donor haplotype

• Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study

Inclusion Criteria Donor:

• Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of the unshared haplotype

• Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for donors under the age of 18 will be followed)

• Eligible for donations of human blood and blood components according to local requirements and regulations

• Eligible for donation according to the transplantation center

Exclusion Criteria Donor:

• Positive pregnancy test or nursing (women of childbearing age only)

• Positive viral test for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV 1 (if tested), HTLV-2 (if tested), or WNV (if tested)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Algemeen Ziekenhuis Sint-Jan	Brugge		Belgium	8000
2	Institut Jules Bordet	Brussels		Belgium	1000
3	Universitair Ziekenhuis Gasthuisberg	Leuven		Belgium	3000
4	Centre Hospitalier Universitaire de Liège	Liège		Belgium	4000
5	Juravinski Hospital and Cancer Centre	Hamilton	Ontario	Canada	L8V 1C3
6	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4
7	University Hospital Centre Zagreb	Zagreb		Croatia	10000
8	University Medical Center Mainz	Mainz		Germany	55131
9	Hospital de Santa Maria, Clinica Universitaria Hematologia	Lisboa		Portugal	1649-028
10	Heartlands Hospital	Birmingham		United Kingdom	B9 5SS
11	Hammersmith Hospital	London		United Kingdom	W12 ONN

Sponsors and Collaborators

• Kiadis Pharma

Investigators

• Principal Investigator: Denis Claude Roy, Prof MD, Maisonneuve-Rosemont Hospital (Montreal, Canada)
• Principal Investigator: Stephan Mielke, Prof MD, Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital (Stockholm, Sweden)

Study Documents (Full-Text)

• Study Protocol - Nov 20, 2015
• Statistical Analysis Plan - Dec 13, 2018

More Information

Publications

None provided.

• Responsible Party: Kiadis Pharma
• ClinicalTrials.gov Identifier: NCT02500550
• Other Study ID Numbers: CR-AIR-008
• First Posted: Jul 16, 2015
• Last Update Posted: May 18, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kiadis Pharma: Haploidentical stem cell transplantation; Graft versus host disease; Immune reconstitution; Alloreactive T-cells; Photodynamic treatment; Hematologic malignancy; Transplant-related mortality
• Additional relevant MeSH terms: Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Myelodysplastic Syndromes

Study Results

Participant Flow

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Period Title: Overall Study
STARTED	15
COMPLETED	8
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Overall Participants	15
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	41
Sex: Female, Male (Count of Participants)
Female	10 66.7%
Male	5 33.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
Canada	7 46.7%
Belgium	5 33.3%
United Kingdom	2 13.3%
Germany	1 6.7%

Outcome Measures

1. Primary Outcome

Title	Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV
Time Frame	180 days post HSCT

Outcome Measure Data

Analysis Population Description

The primary study endpoint, grade III/IV acute GVHD within 180 days after HSCT, was met for two patients treated with two doses of ATIR101. Two patients developed grade III/IV acute GVHD within 180 days after HSCT treated with a single dose of ATIR101.

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Single dose of ATIR101, grade III/IV acute GVHD within 180 days after HSCT	2 13.3%
Two doses of ATIR101, Grade III/IV acute GVHD within 180 days after HSCT	2 13.3%

2. Secondary Outcome

Title	Incidence and Severity of Acute and Chronic GVHD
Time Frame	Between 6 and 12 months after HSCT

Outcome Measure Data

Analysis Population Description

7 patients in the single dose and 4 patients in the double dose were analysed to make a total of 11 patients analysed.

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	11
Single dose group acute GVHD between 6 and 12 months after HSCT	0 0%
Double dose group acute GVHD between 6 and 12 months after HSCT	0 0%
Single dose group chronic GVHD between 6 and 12 months after HSCT	0 0%
Double dose group chronic GVHD between 6 and 12 months after HSCT	2 13.3%

3. Secondary Outcome

Title	Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Description	Defined as CD3+ in peripheral blood higher than 0.2×10E9/L at 6 and 12 months post HSCT.
Time Frame	6 and 12 months post HSCT

Outcome Measure Data

Analysis Population Description

Cumulative incidence estimates of T-cell reconstitution at 6 and 12 months post HSCT were analyzed for the single dose group (N=9) and double dose group (N=6).

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Cumulative incidence estimates of T-cell reconstitution, 6 months post HSCT. Single dose group.	44.4 296%
Cumulative incidence estimates of T-cell reconstitution, 6 months post HSCT. Double dose group.	50.0 333.3%
Cumulative incidence estimates of T-cell reconstitution, 12 months post HSCT. Single dose group.	77.8 518.7%
Cumulative incidence estimates of T-cell reconstitution, 12 months post HSCT. Double dose group.	50.0 333.3%

4. Secondary Outcome

Title	Viral, Fungal, and Bacterial Infections
Description	Infection was defined as (1) a clinically apparent infectious disease with symptoms or (2) a viral reactivation. Severity was graded according to CTCAE vs. 4.0
Time Frame	From 6 months to 1 year after HSCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	11
Any infection	10 66.7%
Severity, grade 1-2	7 46.7%
Severity, grade 3-5	3 20%

5. Secondary Outcome

Title	Transplant-related Mortality (TRM)
Description	Defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide)
Time Frame	12 months post HSCT

Outcome Measure Data

Analysis Population Description

Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Single-dose group, cumulative estimates of TRM	22.2 148%
Double-dose group, cumulative estimates of TRM	66.7 444.7%

6. Secondary Outcome

Title	Relapse-related Mortality (RRM)
Description	Defined as death due to disease relapse or disease progression
Time Frame	12 months post HSCT

Outcome Measure Data

Analysis Population Description

Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Single dose group, cumulative estimates of RRM 12 months post HSCT	11.1 74%
Double dose group, cumulative estimates of RRM 12 months post HSCT	0 0%

7. Secondary Outcome

Title	Overall Survival (OS)
Description	Defined as the time from HSCT until death from any cause
Time Frame	12 months post HSCT

Outcome Measure Data

Analysis Population Description

Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Single dose group, Kaplan-Meier estimates of OS 12 months post HSCT	66.7 444.7%
Double dose group, Kaplan-Meier estimates of OS 12 months post HSCT	33.3 222%

8. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first
Time Frame	12 months post HSCT

Outcome Measure Data

Analysis Population Description

Nine participants received a single dose of ATIR101 and 6 participants received a double dose of ATIR101

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Single dose group, Kaplan-Meier estimates of PFS 12 months post HSCT	55.6 370.7%
Double dose group, Kaplan-Meier estimates of PFS 12 months post HSCT	33.3 222%

9. Secondary Outcome

Title	GVHD-free, Relapse-free Survival (GRFS)
Description	Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first
Time Frame	12 months post HSCT

Outcome Measure Data

Analysis Population Description

Nine subjects received a single dose of ATIR101 and 6 subjects received a double dose of ATIR101.

Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Measure Participants	15
Single dose, Kaplan-Meier estimates of GRFS	55.6 370.7%
Double dose, Kaplan-Meier estimates of GRFS	16.7 111.3%

Adverse Events

Time Frame	The median follow-up time of ATIR101-treated patients in the study was 11.6 (range 2.7-12.8) months after hematopoietic stem cell transplantation (HSCT) .
Arm/Group Title	ATIR101
Arm/Group Description	ATIR101: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons). Haploidentical hematopoietic stem cell transplantation (HSCT): CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: Total Body Irradiation (TBI) regime Non-TBI regime (See below for details) TBI regime: • Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV. Non-TBI regime: • Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
All Cause Mortality
	ATIR101
	Affected / at Risk (%)	# Events
Total	7/15 (46.7%)
Serious Adverse Events
	ATIR101
	Affected / at Risk (%)	# Events
Total	7/15 (46.7%)
Immune system disorders
Acute graft-versus-host disease (GVHD)	5/15 (33.3%)
Chronic GVHD	2/15 (13.3%)
Other (Not Including Serious) Adverse Events
	ATIR101
	Affected / at Risk (%)	# Events
Total	8/15 (53.3%)
Immune system disorders
Acute GVHD	7/15 (46.7%)
Chronic GVHD	2/15 (13.3%)
Investigations
Cytomegalovirus (CMV) positive	1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.